Therapeutic combinations comprising a selective estrogen receptor modulator and prostaglandin E2

Abstract

This invention is directed to pharmaceutical combination compositions and methods comprising (-)-cis-6-phenyl-5-(4-(2-pyrrolidin-1-yl-ethoxy)-phenyl)-5,6,7,8-tetrahydronaphthalene-2-ol or a pharmaceutically acceptable salt thereof and PGE2 or a pharmaceutically acceptable salt thereof, methods of using such compositions and kits containing such compositions. The compositions are useful for treating musculoskeletal frailty, including osteoporosis, osteoporotic fracture, low bone mass and frailty.

What is claimed is:  
     
       1. A pharmaceutical composition comprising: in synergistic effective amounts 
       a. a first compound, said first compound being (−)-cis-6-phenyl-5-(4-(2-pyrrolidin-1-yl-ethoxy)-phenyl)-5,6,7,8-tetrahydronaphthalene-2-ol or a pharmaceutically acceptable salt thereof; and  
       b. a second compound, said second compound being PGE2 or a pharmaceutically acceptable salt thereof.  
     
     
       2. A pharmaceutical composition of claim  1  additionally comprising a pharmaceutical carrier or diluent. 
     
     
       3. A pharmaceutical composition of claim  1  wherein said first compound is (−)-cis-6-phenyl-5-(4-(2-pyrrolidin-1-yl-ethoxy)-phenyl)-5,6,7,8-tetrahydronaphthalene-2-ol D-tartrate and said second compound is PGE2. 
     
     
       4. A method for treating a mammal suffering from musculoskeletal frailty comprising administering to said mammal a pharmaceutical composition of claim  1 . 
     
     
       5. A method of claim  4  wherein said first compound is (−)-cis-6-phenyl-5-(4-(2-pyrrolidin-1-yl-ethoxy)-phenyl)-5,6,7,8-tetrahydronaphthalene-2-ol D-tartrate and said second compound is PGE2. 
     
     
       6. A method of claim  4  wherein said mammal is suffering from osteoporosis. 
     
     
       7. A method of claim  4  wherein said mammal is suffering from osteotomy, childhood idiopathic bone or bone loss associated with periodontitis. 
     
     
       8. The method of claim  4  wherein bone fracture, bone healing following facial reconstruction, maxillary reconstruction or mandibular reconstruction is treated, vertebral synostosis is induced or long bone extension is enhanced, the healing rate of a bone graft is enhanced or prosthetic ingrowth is enhanced. 
     
     
       9. The method of claim  8  wherein a bone fracture is treated in a human. 
     
     
       10. A method of claim  6  wherein osteoporosis is treated in a human. 
     
     
       11. A method for treating a mammal suffering from musculoskeletal frailty comprising administering to said mammal 
       a. a first compound, said first compound being (−)-cis-6-phenyl-5-(4-(2-pyrrolidin-1-yl-ethoxy)-phenyl)-5,6,7,8-tetrahydronaphthalene-2-ol or a pharmaceutically acceptable salt thereof; and  
       b. a second compound, said second compound being PGE2 or a pharmaceutically acceptable salt thereof.  
     
     
       12. A method of claim  11  wherein the first compound and the second compound are administered substantially simultaneously. 
     
     
       13. A method of claim  11  wherein the second compound is administered for a period of from about three months to about three years. 
     
     
       14. A method of claim  13  followed by administration of the first compound for a period of from about three months to about three years without the administration of the second compound during the period of from about three months to about three years. 
     
     
       15. A method of claim  13  followed by administration of the first compound for a period greater than about three years without the administration of the second compound during the greater than about three year period. 
     
     
       16. A method of claim  11  wherein said mammal is suffering from osteoporosis. 
     
     
       17. A method of claim  16  wherein said mammal is a human. 
     
     
       18. A method of claim  11  wherein said mammal is suffering from osteotomy, childhood idiopathic bone loss or bone loss associated with periodontitis. 
     
     
       19. The method of claim  11  wherein bone fracture, bone healing following facial reconstruction, maxillary reconstruction or mandibular reconstruction is treated, vertebral synostosis is induced or long bone extension is enhanced, the healing rate of a bone graft is enhanced or prosthetic ingrowth is enhanced. 
     
     
       20. The method of claim  19  wherein a bone fracture is treated in a human. 
     
     
       21. A kit comprising: 
       a. (−)-cis-6-phenyl-5-(4-(2-pyrrolidin-1-yl-ethoxy)-phenyl)-5,6,7,8-tetrahydronaphthalene-2-ol or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or diluent in a first unit dosage form;  
       b. PGE2 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or diluent in a second unit dosage form; and  
       c. a container.  
     
     
       22. A kit of claim  21  wherein said first unit dosage form comprises (−)-cis-6-phenyl-5-(4-(2-pyrrolidin-1-yl-ethoxy)-phenyl)-5,6,7,8-tetrahydronaphthalene-2-ol D-tartrate and said second unit dosage form comprises PGE2.